Tag Archives: MTHFR a1298C

MTHFR mutation discussions can quickly turn into Greek and the topic of overmethylated vs undermethylated MTHFR is one of the Greekest. It seems like no two resources on the internet are talking about the same thing when they talk about it and so overmethylation and undermethylation are strange, kind of meaningless words because at the end of the day it feels like nailing jello to a wall. So let’s see if we can sort some of this out.

Whose Idea Is This? I’m Following The Walsh Research Institute

The terms overmethylation and undermethylation make the most sense to me as the Walsh Research Institute uses them. These are general physical tendencies based on the sum of your genetics, nutritional status and body burden. There isn’t one gene or genetic defect alone that can account for them – so just because you have an MTHFR C677T mutation doesn’t actually mean you’re over or under methylated (although it would be one factor that might push the balance to undermethylation). Dr. Walsh describes one’s methylation status as being like a tug of war between opposing factors. Many of those are genetic and some are nutritional or environmental.

Undermethylation MTHFR

This is the most common state. According to Dr. Walsh’s research, 70% of the population are normal methylators, 22% are undermethylators and 8% are overmethylators. Undermethylation indicates that the methylation cycle as a whole is slowed down enough that the end product, SAMe, is typically inadequate and thus causes symptoms.

Clinically undermethylators are more commonly autism spectrum (98% of autism spectrum clients at the Walsh Research Institute), antisocial disorder (95% of antisocial clients at WRI were undermethylators), schizoaffective disorder (90%), oppositional defiant disorder (85%), anorexia (82%), and depression (which can occur in under, normal or over methylators but 38% of depressed clients for Dr. Walsh are undermethylators).

Mutations most likely to contribute to undermethylation are MTHFR (C677T especially, but also A1298C), MS, BHMT, MAT and SAHH. Remember that the presence of one or more of these mutations isn’t enough to say if you’re an over or under methylator. The combination of all of your genetic factors as well as your nutritional state must be taken into account. The best way to determine is through symptoms and traits.

Other contributing factors are histamine overload and protein deficiency, as well as frank deficiency of folate.

Highly competitive? You might be undermethylated

Symptoms and traits of undermethylation include:

Strong willed

Highly competitive at sports or whatever matters to them

Obsessive/compulsive tendencies

Addictive tendencies (more likely to be addicted with less exposure than a normal methylator)

High sex drive

Tend towards high accomplishment and usually a high achieving family

Appear calm and well controlled (possibly over-controlled) but inner tension is high

Is Undermethylated the Same as Under-supplemented?

No! Although it seems that in a lot of popular literature on the subject people use the term interchangeably. So often you’ll see someone say that you might still be “undermethylated” if you aren’t taking enough 5-MTHF. I feel that these are different things entirely. If you have a tendency to be undermethylated then certainly you will probably need to take 5-MTHF, but even once you’re taking enough you are still an undermethylator (in my opinion), you’re just taking the right protocol. Likewise taking too much 5-MTHF, doesn’t make you suddenly “overmethylated” it just means you’re taking too much.

Okay! I’m Undermethylated. Now What?

Absolutely the best way to enhance the methylation cycle is by taking 5-MTHF, or 5-L methyltetrahydrofolate. This is the active form of folic acid, and you can also get it from foods, especially if you have some trouble taking the supplement. Trouble taking the supplement is surprisingly common, typically it is an adjustment reaction to actually enhancing the methylation cycle because this changes neurotransmitter levels, encourages detoxification and encourages more than 80 reactions in the body that are methylation dependent. So some adjustment reaction when you’re first taking 5-MTHF is normal and actually a good sign that things are changing in your body. There is one BIG EXCEPTION TO THIS, and that is if you are undermethylated and have depression.

I Want to Start Taking 5-MTHF. How Do I Make This Easy?

Any time you start taking 5-MTHF, or increase your dose, there will be an adjustment period. Here’s a whole post on it. Just remember, start with a low dose and increase really slowly. This is changing the way your neurotransmitters work and doing some heavy detox work, so it’s vital not to overdo it because that is crazy-making. Start low and go slow.

HELP! I’m An Undermethylator and I Have Depression.

My next post is going to be all about this because UNDERMETHYLATORS WITH DEPRESSION DUE TO LOW SEROTONIN CAN’T TOLERATE 5-MTHF, FOOD SOURCES OF FOLATE OR FOLIC ACID AT ALL. That’s a really big deal! Depression is typically characterized by low serotonin states and unfortunately 5-MTHF (or any folate or folic acid). The short explanation for this is that folate, 5-MTHF and folic acid all increase the activity of the transport protein that re-uptakes serotonin into the cell. Essentially this is the opposite of a serotonin reuptake inhibitor (like prozac), it’s a serotonin reuptake promotor – meaning it makes the serotonin you have far less effective because it clears it out more quickly. There will be a whole post on this – I promise!

MTHFR mutations are just starting to be recognized as an issue and so more and more doctors are testing, but what happens if your doctor tells you that you’re homozygous for MTHFR A1298C? They might as well be speaking Greek! So here’s the skinny on what that really means. Also here’s a post about MTHFR mutation basic in general.

MTHFR A1298C Terminology Basics (or as basic as we’re going to get with genetics).

The simplest level of information here is just the plain genetics. Here are some quick factoids to get us started:

MTHFR is the short name for the genes that code for the enzyme that changes folic acid to the active form that your body uses (the long name is methylfolate reductace).

1298 is the marker for one particular MTHFR gene.

The official genetics labeling of this gene is Rs1801131. Sigh.

You get one copy of this gene from your mother and one from your father, so there are two possible copies that can be either “normal” or “mutant”

If you inherited one good copy and one bad copy that’s called “heterozygous A1298C”

If you inherited two bad copies (one from each parent) that’s called “homozygous A1298C”

A…C stand for the bases that you actually have. A = adenine C = cytosine. Bases are essentially the letters that spell out your genetic code. There are four of them commonly (C, T, A and G).

When this gene is “normal”or “wild type” (I love that name) it looks like MTHFR A1298A.

Heterozygous mutations (one good copy and one bad) are MTHFR A1298C because there is one normal A and one abnormal C Also occasionally written 1298AC.

Homozygous A1298C (two bad copies) can also be written as C1298C (because there are two abnormal copies with C instead of A). Occasionally you’ll also see it written 1298CC

Phew! So the take-away there is MTHFR A1298C means you have at least one bad copy of this gene, and if it’s called homozygous, or C1298C then you have two bad copies.

How Much of a Problem Is This?

The MTHFR A1298C mutation is considered less serious than the C677T mutation because it seems to cause less impairment to actual methylation function than C677T. That doesn’t in any way mean that it isn’t an issue. This mutation can still be a significant problem If you don’t have a good diet, don’t take supplements or burden your body with a lot of stressors like smoking, alcohol, drugs, sedentary lifestyle or high stress. If you get lots of dark green leafy veggies, legumes and other food sources of natural folate – see this post – then you’re probably already getting good methylfolate. If your diet isn’t up to scratch, then supplementation can be useful and here’s a whole post about that.

Heterozygous MTHFR A1298C is thought to have mostly normal MTHFR activity and homozygous MTHFR A1298C (C1298C) have about 65% normal activity (so 35% compromise). Normal activity refers to the way your body converts folic acid to 5-L-methyltetrahydrafolate (the active form) so that it can be used. Compromise in this case looks like a folate deficiency.

What Are The Health Risks of MTHFR A1298C Mutation?

According to SNPedia, which compiles research on genetics, A1298C mutants have been shown in at least one research study to have an increased risk for:

Midline defects such as:

Cleft lip

Cleft palate

Neural tube defects

Facial asymmetries

Cancers including:

Breast

Lung

Brain

Stomach

Head and neck

Kidney

Cardiac-related issues including:

Thrombosis (increased tendency to clot inappropriately)

High homocysteine levels (a heart risk)

Pre-eclampsia (dangerous high blood pressure in pregnancy)

Vascular dementia

Fertility issues including:

Multiple pregnancy loss

Low sperm count

Birth defects such as down syndrome

Neurological issues including:

Migraines

Autism

Alzheimer’s dementia

Mood and psychological issues including:

Depression

Anxiety

Schizophrenia

You’ll notice that this is quite a list, and it can be a little daunting to think about when you’re just learning about this. Most research doesn’t differentiate between the A1298C genetic variance and the C677T genetic variance so the list is the same for both mutations. We assume the risk is lower with A1298C because the folate metabolism is less strongly impaired, but that might not be correct.

What Do You Do About This?

Compromise with the MTHFR A1298C gene can have severe consequences so it’s important to work on getting good sources of natural folate from foods, which is generally useable by mutants, or 5-MTHF (5-methyltetrahydrofolate) which is already methylated so the genetic compromise doesn’t matter. As discussed in this article, I feel supplementation should be started slowly because for many mutants who haven’t had active folate very much in their lives it feels really strange when those active forms start showing up. There can be quite an adjustment reaction by your body.

Activated folate is used by your body to run enzyme pathways, to aid in some parts of normal metabolism, to help your body detoxify and even to methylate your DNA. The methylation cycle is also a big part of neurotransmitter manufacture, which explains the strong link to depression, anxiety, and mental disorders including addictions and even schizophrenia. If 5-Methylfolate isn’t there then your body does maintains those functions as best it can, but the things your body can’t do start to pile up. Starting supplementation means your body can start digging in that pile to clear up high priority items. This is exactly what we want, but if you start with high doses of a supplement then it’s a little like drinking from the firehose. Kind of out of control and not very pleasant.

A great way to start if you’re unsure, is with a folate-rich diet. I love this image because it kind of covers what we’re looking for. Hint – think dark greens and beans. 🙂

Is folate in foods safe in MTHFR mutants? In these foods YES! For MTHFR C677T or MTHFR A1298C mutants. Thanks to exhibithealth.com for the great image.

Can Mutants Become “Normal”?

If you’re a mutant (like me) then you’ll always be a mutant, but it doesn’t have to matter. Essentially as long as you’re getting enough of the active form of folate and taking care of yourself for the other consequences of the MTHFR mutation then the mutation doesn’t have to matter. If you aren’t taking care of yourself, then it matters a lot.

The bottom line is MTHFR A1298C mutations don’t have to mean anything at all as long as you supplement and have a good diet and lifestyle (here’s an article about a folate-rich diet for MTHFR mutants) I always suggest taking a little more care with yourself too. There are known health risks for things like clotting, fertility and cancers so it makes sense to take some precautions. Eat your fiber, do your exercises, get your sleep and generally treat yourself with high regard – shouldn’t we all anyway?

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Amy Neuzil is a Health Coach and Naturopath and not a Medical Doctor or Doctor of Osteopathy. All information on dramyneuzil.com is written from a naturopathic perspective. While Amy and dramyneuzil.com strive to have the most accurate information possible, we do not provide medical or health care advice. Please consult your physician before starting any new supplements or treatments and for any medical questions you may have.